The physical properties (solidity, hemoglobin composition, molecular structure) of gels formed from pure sickle hemoglobin will be compared with the physical properties of gels formed from mixtures of sickle and non-sickle hemoglobins. Pathogenesis in sickle cell disease depends on the polymerization of deoxyhemoglobin S into long fibers followed by "gel" formation. The deoxyhb S gel leads to impaired red cell deformability and sickling, with consequent chronic hemolysis and occlusion of the microcirculation. Briehl1,2 has demonstrated by in vitro studies that the behavior of deoxyhb S gels is in conformity with the definition of a solid. No studies have been made of gels resulting from mixtures of sickle with non-sickle hemoglobins or of gels formed under varying conditions of oxygen saturation. Although in considering pathophysiologic mechanisms, many workers have assumed similar gel (polymer) structures in mixed and pure deoxyhb S gels (and therefore similar physical properties, i.e., solidity), there are other indications that the molecular structures of mixed hemoglobin polymers do differ from those of pure deoxy S, and that structures of pure S hb polymers formed at intermediate oxygen saturations are different from those formed in deoxygenate solutions. Demonstrable differences in the solid behaviors of deoxygenated pure S and mixed hemoglobin gels and of gels formed at intermediate oxygen saturations, as determined by viscosity studies of gels, will indicate differences in the molecular structures. In addition, by combining ultra-centrifugation of gels (to separate the hemoglobins remaining in supernatant from polymer) with isoelectric focusing (to quantitate the hemoglobin components of supernatant and polymer), the effects of non-S and oxy S hemoglobins on deoxyhb S solubility and the extent of their incorporation into the polymer will be measured. These studies will provide the first data about the solidity (structure) of mixed hemoglobin gels and gels formed under different conditions of oxygen saturation. Information about proportions and types of hbs incorporated into polymers and their rheologic behavior have great importance 1) as evidence for different physical properties and molecular structures of the gels, 2) in understanding the pathophysiology of various sickling disorders, and 3) in planning therapeutic interventions.